Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis - A randomized, double-blind, placebo-controlled trial
Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis - A randomized, double-blind, placebo-controlled trial
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DOI：
10.7326/0003-4819-137-11-200212030-00008
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发表时间：
2002-12-03
影响因子：
39.2
通讯作者：
Lombardi, A
中科院分区：
文献类型：
--
作者：
Greenspan, SL;Emkey, RD;Lombardi, A
背景资料：阿仑膦酸钠和雌激素联合治疗2年，增加脊柱和髋关节的骨密度比单独使用任何一种药物治疗都要多。停药后骨密度的变化尚未直接比较。目的：确定阿仑膦酸钠、雌激素或两者联合治疗停药后的骨丢失率。设计：双盲、安慰剂对照停药试验。设置：18个美国中心。患者：244例绝经后、卵巢切除的44 - 77岁妇女，干预：阿仑膦酸钠10 mg/d（n = 92）、结合雌激素0.625 mg/d（n = 143）、阿仑膦酸钠和结合雌激素（n = 140）或安慰剂（n = 50）治疗2年。在第3年，这些妇女被分为5组：28名妇女继续服用安慰剂，44名妇女继续服用联合治疗，但50名妇女服用阿仑膦酸钠，81名妇女服用结合雌激素，41名妇女服用联合治疗后转为服用安慰剂。测量：骨密度和骨转换的生化标志物。服用阿仑膦酸钠或联合治疗的妇女在研究的第3年转换为安慰剂，保持了骨量。这些妇女的骨密度为4.1%，（Cl，2.6%至5.7%）和6.6%（Cl，5.0%-8.2%）分别在脊柱处升高（两种治疗比较P < 0.001）和3.5%与之前服用雌激素而改用安慰剂的妇女相比，在转子处的CI分别为2.3%至4.6%和3.0%（CI为1.8%至4.2%）（两种治疗比较P < 0.001）。相反，服用雌激素并在第3年转换为安慰剂的妇女脊柱下降4.5%（95%CI，-5.0%至4.0%），转子下降2.4%（CI，-2.7%至2.1%）（两种变化均P < 0.001）。与服用安慰剂3年的女性相比，服用雌激素2年然后改用安慰剂的女性脊柱骨密度高2.9%（CI，1.2%至4.6%）（P < 0.05），转子骨密度高2.9%（CI，1.6%至4.2%）（P < 0.001）。在第3年的生化标志物的变化并没有不同的组之间，停止积极的treatment.Conclusions：加速骨丢失后，雌激素治疗，但不撤回阿仑膦酸钠或联合治疗。在绝经后骨质疏松症的治疗中，应考虑停药后的不同影响。
Background: Combination therapy with alendronate and estrogen for 2 years increases bone mineral density at the spine and hip more than does therapy with either agent alone. Changes in bone mineral density after discontinuation of therapy have not been compared directly.Objective: To determine the rate of bone loss when therapy with alendronate, estrogen, or both agents is discontinued.Design: Double-blind, placebo-controlled discontinuation trial.Setting: 18 U.S. centers. Patients: 244 postmenopausal, hysterectomized women 44 to 77 years of age.Intervention: 2 years of therapy with alendronate, 10 mg/d (n = 92); conjugated estrogen, 0.625 mg/d (n = 143); alendronate and conjugated estrogen (n = 140); or placebo (n = 50). At year 3, women were allocated into five groups: Twenty-eight women continued to take placebo and 44 women continued to take combination therapy, but 50 women taking alendronate, 81 taking conjugated estrogen, and 41 taking combination therapy were switched to placebo.Measurements: Bone mineral density and biochemical markers of bone turnover.Results: Women taking alendronate or combination therapy who were switched to placebo for year 3 of the study maintained bone mass. Bone mineral density in these women was 4.1 % (Cl, 2.6% to 5.7%) and 6.6% (Cl, 5.0% to 8.2%) higher, respectively, at the spine (P < 0.001 for both treatment comparisons) and 3.5% (Cl, 2.3% to 4.6%) and 3.0% (Cl, 1.8% to 4.2%) higher, respectively, at the trochanter (P < 0.001 for both treatment comparisons) than that in women previously taking estrogen who were switched to placebo. in contrast, women who were taking estrogen and were switched to placebo during year 3 experienced a 4.5% decrease at the spine (95% Cl, -5.0% to -4.0%) and a 2.4% decrease at the trochanter (Cl, -2.7% to -2.1 %) (P < 0.001 for both changes). Compared with women who took placebo for 3 years, women who took estrogen for 2 years and were then switched to placebo had a bone mineral density that was 2.9% higher (Cl, 1.2% to 4.6%) at the spine (P < 0.05) and 2.9% higher (Cl, 1.6% to 4.2%) at the trochanter (P < 0.001). Changes in biochemical markers during year 3 did not differ among the groups that discontinued active treatment.Conclusions: Accelerated bone loss is seen after withdrawal of estrogen therapy but not after withdrawal of alendronate or combination therapy. The differential effects after withdrawal of therapy should be considered in the management of postmenopausal osteoporosis.